In this project, SPECT perfusion data will be obtained at baseline from controls and non-demented subjects with cognitive impairments who will be recruited through the Clinical Core and followed over time. Subjects will be evaluated longitudinally with SPECT when they cross specific transition boundaries, as defined by the Clinical Core. The overall goal of the SPECT project is to determine whether SPECT data can be used to predict which non-demented individuals with cognitive problems will develop progressive cognitive decline, which will progress to the point where they meet criteria for AD, and which will remain stable. In addition, we will seek to determine the evolution of brain changes that characterize prodromal AD, and how these measures relate to the clinical characteristics of the subjects. Underlying these goals is the assumption that SPECT perfusion data can serve as an indirect measure of the neuronal loss that occurs when neuritic plaques and neurofibrillary tangles accumulate during the development of Alzheimer's disease (AD). In the proposed funding cycle we will analyze the SPECT data with several methods: (1) MRI guided regions-of-interest (ROI), (2) a multivariate, voxel-based method known as singular value decomposition (SVD), and (3) a widely used voxel-based unvariate method, statistical parametric mapping (SPM99). Results from the three processing streams will be compared with one another and to variables from other projects and cores. In addition, we will seek to determine the relationship between SPECT measures and other information obtained on the same individuals by the cores and the projects, including clinical data, genotype status, volumetric MRI, and fMRI signal change.